Analysis of ETFDH gene variation in a Chinese family affected with lipid storage myopathy / 中华医学遗传学杂志

Objective@#To detect potential variation in an ethnic Han Chinese family affected with late-onset lipid storage myopathy.@*Methods@#Next generation sequencing (NGS) was used to screen disease-related genes in the proband. Suspected mutation was validated with PCR and Sanger sequencing in two patients, their father, and 100 healthy controls.@*Results@#Heterozygous c. 770A>G (p.Tyr257Cys) and c. 1395dupT (p.Gly466Tryfs) mutation were detected in the two patients. Their father was found to be heterozygous for the c. 770A>G (p.Tyr257Cys) mutation, while the c. 1395dupT (p.Gly466Tryfs) variation was not reported previously and not found among the healthy controls.@*Conclusion@#Mutations of the ETFDH gene probably underlie the pathogenesis in this family. The novel c. 1395dupT (p.Gly466Tryfs) has enriched the mutation spectrum of EDFDH gene.

Lipid storage myopathy / 中华神经科杂志

Lipid storage myopathy (LSM) is an etiologically heterogeneous group of lipid metabolic disorders characterized by accumulation of light microscopic lipid droplets in muscle fibers.This disease seems to be more common in Chinese population accounting for 3％-5％ of total muscle biopsies in several large neuromuscular centers in China.The pathogenesis of LSM is the impairment of fatty acid oxidation in muscle fibers.Late-onset multiple acyl-coenzyme A dehydrogenase deficiency (MADD) caused by electron transfer flavoprotein dehydrogenase (ETFDH) gene mutation has been demonstrated to be the main molecular defect in China.Three frequent ETFDH mutations were identified:c.250G＞A in patients from South China,and c.770A＞G and c.1227A＞C in those from both South and North China.More importantly,almost all late-onset MADD are dramatically responsive to riboflavin supplementation.Neutral lipid storage disease with myopathy (NLSDM) caused by mutations in PNPLA2 gene is the second common cause of Chinese LSM.Distal muscle involvement and asymmetrical muscle weakness and atrophy are common in primary symptoms of NLSDM which may be the first clue indicating the diagnosis of NLSDM.There were also a few case reports showing that LSM may be caused by carnitine transport defect and other deficiencies of acyl-coenzyme A dehydrogenase involved in fatty acid beta oxidation.Increased lipid droplets accumulation in muscle fibers may also be a secondary consequence of mitochondrial myopathy (mtDNA depletion syndrome or MELAS),dermatomyositis and steroid treatment.

Clinical and pathological characteristics of riboflavin-reactive lipid storage myopathy / 临床神经病学杂志

Objective To investigate the clinical and pathological features of riboflavin-reactive lipid storage myopathy.Methods Clinical material of 4 patients with riboflavin-reactive lipid storage myopathy were analyzed retrospectively.Results All the patients were subacute onset and presented proximal and axial muscle weakness accompanied by intolerance to excise.Amyotrophy and weakness involved in neck and paraspinal muscle were found in 3 cases,and chewing muscle weakness in 2 cases.Electromyogram showed myogenic changes in 2 cases and reduced conductive velocity of tibial nerves in 1 case.Muscle Biopsy study showed markedly increased lipid droplets in muscle fibers.The ragged red fibers,succinate dehydrogenase strongly reactive vessels and COX deficiency fibers which supported mitochondrial myopathy were not detected.Electromicroscope observation revealed that the structure and quantity of mitochondria were normal.All the patients had a dramatic response to riboflavin treatment.Two cases were cured and the other two were improved significantly.Two cases relapsed 1 year and 5 years later,respectively,and riboflavin was still effective for them.Conclusions Riboflavin-reactive lipid storage myopathy is a myopathy characterized by preferential involvement of neck,paraspinal and chewing muscles.The distinct pathological features are lipid accumulation in muscle fibers without any abnormalities of mitochondrial structure and quantity.Riboflavin alone is effective for this myopathy and this is distinguished from other myopathies.

Clinical and pathological features of lipid storage myopathy caused by primary carnitine deficiency / 临床神经病学杂志

Objective To analyze the clinical and pathological features of lipid storage myopathy (LSM) caused by primary carnitine deficiency (CD).Methods The clinical data of 4 cases of possible LSM caused by primary CD were analyzed retorspectively.Results The clinical features of the 4 patients were subacute or chronic onset, proximal muscle weakness and exercise intolerance. Elevated levels of creatases were measured in serum and myogenic damage was found by EMG examination. Frozen sections of muscle biopsy samples showed many fibers contained numerous vacuoles which was stained by oil red O. No ragged red fiber (RRF) was seen in MGT stain. Type I fibers were more severely affected. In electron microscopy, the prominent abnormality was the presence of excessive amounts of fatty droplets in muscle fibers and subsarcolemmal regions with mild increased mitochondria.Treatment with glucocorticoid and energy supplement had been clinically beneficial. Conclusions Fatigue and muscle weakness are prominent manifestations in LSM caused by primary CD. The main changes are accumulation of lipid droplets in muscle specimen without prominent abnormality in structure in mitochondria. Good clinic effect may be caused by therapy with glucocorticoid.